The relationships aren't strong enough to have immediate prognostic value, but they suggest that markers predictive of neuropsychiatric episodes could be identified in the future, said John G. Hanly, M.D., of the Nova Scotia Rehabilitation Center, and colleagues in the March issue of Arthritis & Rheumatism.

Up to 95% of lupus patients suffer some type of neurologic or psychiatric event, the researchers said. These may include strokes, seizures, psychosis, mood disorders, cognitive dysfunction, and neuropathies.

However, the relationships between these events and the underlying autoimmune process have not been well-studied, they said. They undertook the current study in hopes of linking particular types of autoimmunity to particular neuropsychiatric episodes early in the development of lupus.

The international, multi-center study recruited 412 patients recently diagnosed with lupus. From the patients' records, the investigators identified all neuropsychiatric events occurring from six months before the diagnosis up to enrollment, a mean of 11 months.

Events were classified according to American College of Rheumatology criteria for 19 neuropsychiatric syndromes. Repeated episodes of the same type of event were counted only once.

Following review by the investigators, specific episodes were determined to be related or not related to lupus according to two sets of rules, one more stringent than the other.

A total of 214 events were identified in 133 patients. The investigators ruled that 137 of the events were not related to lupus according to both sets of rules. Of these, 86 were headaches and 17 were anxiety disorders.

The presence of anti-ribosomal P antibodies was significantly associated with central neuropsychiatric events determined to be lupus-related by the least stringent criteria.

Four of 20 patients (20%) with these events had these antibodies, versus 3 of 107 patients (3%) with non-lupus related central events and 24 of 279 patients (8.6%) who did not have neuropsychiatric events (P=0.04).

Anti-ribosomal P antibodies were also significantly related to diffuse lupus-related events by the same criteria, seen in three of 11 of patients versus four of 111 patients with non-lupus related diffuse events and 24 of 279 patients with no events (P=0.02).

This same group of antibodies was also significantly associated with lupus-related psychosis (P=0.02), the researchers said.

The only other type of autoantibody for which the investigators found a significant link to neuropsychiatric events was the lupus anticoagulant antibody, an anti-phospholipid species.

Its presence was correlated with cerebrovascular disease: six of 14 patients (43%) experiencing cerebral ischemic episodes including strokes and chronic multifocal disease had the antibodies, compared with 52 of 279 patients (19%) without neuropsychiatric events (P=0.038).

However, for both anti-ribosomal P and lupus anticoagulant antibodies, the sensitivity is too low for them to be used clinically, the researchers said.

They also acknowledged that their methods for identifying neuropsychiatric events and ascribing them to lupus versus other causes were imperfect.

In addition, they measured autoantibodies only once, so that some transient autoantibodies may have been missed, they said.

"Despite these limitations, this study provides novel information on the prevalence of specific autoantibodies in an international [lupus] inception cohort," the researchers wrote.

They said they planned follow-up studies in a larger sample of newly diagnosed patients. This research will be powered to examine whether lupus autoantibodies predict later development of neuropsychiatric events or their course.

The study was supported by the Canadian Institutes of Health Research, the Capital Health Research Fund, the Lupus Foundation of Ontario, the Ontario Lupus Association, Lupus UK, the Lupus Foundation of America, the Conn Smythe Foundation, the Tolfo Family, the Arthritis Research Campaign, the Wellcome Trust, Brain Korea 21 Program, Singer Family Fund for Lupus Research, Arthritis Center of Excellence, the National Institutes of Health, and the Swedish Medical Research Council.

Authors of the study reported financial relationships with UCB Pharmaceuticals and Aspreva Pharmaceuticals.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

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